Yuran Hua

Click chemistry generates privileged CH hydrogen-bonding triazoles: the latest addition to anion supramolecular chemistry

The supramolecular chemistry of anions provides a means to sense and manipulate anions in their many chemical and biological roles. For this purpose, Click chemistry facilitated the synthetic creation of new receptors and thus, an opportunity to aid in the recent re-examination of CH...anion hydrogen bonding. This tutorial review will focus on the privileged C-H hydrogen bond donor of the 1,2,3-triazole ring systems as elucidated from anion-binding studies with macrocyclic triazolophanes and other receptors. Triazolophanes are shape-persistent and planar macrocycles that direct four triazole and four phenylene CH groups into a 3.7 A cavity. They display strong (log K(Cl(-)) = 7), size-dependent halide binding (Cl(-) > Br(-) >> F(-) >> I(-)) and a rich set of binding equilibria. For instance, the too large iodide (4.4 A) can be sandwiched between two pyridyl-based triazolophanes with extreme positive cooperativity. Computational studies verify the triazoles hydrogen bond strength indicating it approaches the traditional NH donors from pyrrole. These examples, those of transport, sensing (e.g., ion-selective electrodes), templation, and versatile synthesis herald the use of triazoles in anion-receptor chemistry.

Flipping the switch on chloride concentrations with a light-active foldamer.

Here we demonstrate a bioinspired system where light stimulus is used to trigger the wavelength-dependent release and then reuptake of chloride ions in nonaqueous solutions. A chiral aryl-triazole foldamer with two azobenzene end groups has been synthesized to define a folded binding pocket for chloride ions that unfolds with UV light to liberate the chloride. The trans-dominated helical foldamer becomes less stable upon photoisomerization to the cis forms. Simultaneously, the observed binding affinity shows an ∼10-fold reduction from K = 3000 M(-1) (MeCN, 298 K). Control of chloride levels using light is demonstrated by switching the conductivity of an electrolyte solution up and down.

Intramolecular hydrogen bonds preorganize an aryl-triazole receptor into a crescent for chloride binding.

Aryl-triazole pentads have been preorganized with intramolecular hydrogen bonds to enhance chloride binding. This outcome highlights the dual hydrogen bond donor and acceptor properties of 1,2,3-triazoles.

Aromatic and Aliphatic CH Hydrogen Bonds Fight for Chloride while Competing Alongside Ion Pairing within Triazolophanes

Triazolophanes are used as the venue to compete an aliphatic propylene CH hydrogen-bond donor against an aromatic phenylene one. Longer aliphatic C-H...Cl(-) hydrogen bonds were calculated from the location of the chloride within the propylene-based triazolophane. The gas-phase energetics of chloride binding (ΔG(bind) , ΔH(bind) , ΔS(bind) ) and the configurational entropy (ΔS(config) ) were computed by taking all low-energy conformations into account. Comparison between the phenylene- and propylene-based triazolophanes shows the computed gas-phase free energy of binding decreased from ΔG(bind) =-194 to -182 kJ mol(-1) , respectively, with a modest enthalpy-entropy compensation. These differences were investigated experimentally. An (1) H NMR spectroscopy study on the structure of the propylene triazolophanes 1:1 chloride complex is consistent with a weaker propylene CH hydrogen bond. To quantify the affinity differences between the two triazolophanes in dichloromethane, it was critical to obtain an accurate binding model. Four equilibria were identified. In addition to 1:1 complexation and 2:1 sandwich formation, ion pairing of the tetrabutylammonium chloride salt (TBA(+) ⋅Cl(-) ) and cation pairing of TBA(+) with the 1:1 triazolophane-chloride complex were observed and quantified. Each complex was independently verified by ESI-MS or diffusion NMR spectroscopy. With ion pairing deconvoluted from the chloride-receptor binding, equilibrium constants were determined by using (1) H NMR (500 μM) and UV/Vis (50 μM) spectroscopy titrations. The stabilities of the 1:1 complexes for the phenylene and propylene triazolophanes did not differ within experimental error, ΔG=(-38±2) and (-39±1) kJ mol(-1) , respectively, as verified by an NMR spectroscopy competition experiment. Thus, the aliphatic CH donor only revealed its weaker character when competing with aromatic CH donors within the propylene-based triazolophane.

Triazolophanes: a new class of halide-selective ionophores for potentiometric sensors.

Triazolophanes, cyclic compounds containing 1,2,3-triazole units, are a new class of host molecules that demonstrate strong interactions with halides. These molecules are designed with a preorganized cavity that interacts through hydrogen bonding with spherical anions, such as chloride and bromide. We have explored the use of one such triazolophane as a halide-selective ionophore in poly(vinyl chloride) (PVC) membrane electrodes. Different membrane compositions were evaluated to identify concentrations of the ionophore, plasticizer, and lipophilic additive that give rise to the best chloride and bromide selectivity. The lipophilicity of the plasticizer was found to have a great impact on the electrode response. Additionally, the concentration of the lipophilic additive was found to be critical for optimal response. The utility of a triazolophane-based electrode was demonstrated by quantification of bromide in horse serum samples.

From Atomic to Molecular Anions: A Neutral Receptor Captures Cyanide Using Strong CH Hydrogen Bonds

The multifaceted character of cyanide as an acceptor of hydrogen bonds from a receptor has been examined for the first time using electronic-structure theory and spectroscopic measurements (UV/Vis and NMR titrations). Motivated by the similar size and charge of the cyanide pseudohalide and the monoatomic chloride ion, strong interactions of cyanide with a rigid macrocyclic triazolophane receptor have been predicted by theory and confirmed by experimental findings. It was found that both anions bind with similar strength in the gas phase (computed) and in the solution phase (experimental) via C-H hydrogen bonds. Theoretical calculations predict that the heterodiatomic cyanide prefers to bind in the plane of the macrocycle along the north-south axis. Examination of the possible binding modes reveal low computed barriers for in-plane rotation. The predicted model is consistent with the experimental data. Overall, the binding of a molecular anion within the cavity of a triazolophane receptor has been characterized where the computed and experimental binding energies are consistent with the classification of cyanide as a pseudohalide in the context of supramolecular chemistry.

An Overlooked yet Ubiquitous Fluoride Congenitor: Binding Bifluoride in Triazolophanes Using Computer-Aided Design

Despite its ubiquity during the binding and sensing of fluoride, the role of bifluoride (HF2(-)) and its binding properties are almost always overlooked. Here, we give one of the first examinations of bifluoride recognition in which we use computer-aided design to modify the cavity shape of triazolophanes to better match with HF2(-). Computational investigation indicates that HF2(-) and Cl(-) should have similar binding affinities to the parent triazolophane in the gas phase. Evaluation of the binding geometries revealed a preference for binding of the linear HF2(-) along the north-south axis with a smaller Boltzmann weighted population aligned east-west and all states being accessed rapidly through in-plane precessional rotations of the anion. While the (1)H NMR spectroscopy studies are consistent with the calculated structural aspects, binding affinities in solution were determined to be significantly smaller for the bifluoride than the chloride. Computed geometries suggested that a 20° tilting of the bifluoride (stemming from the cavity size) could account for the 25-fold difference between the two binding affinities, HF2(-) < Cl(-). Structural variations to the triazolophanes geometry and electronic modifications to the network of hydrogen bond donors were subsequently screened in a stepwise manner using density functional theory calculations to yield a final design that eliminates the tilting. Correspondingly, the bifluorides binding affinity (K ∼ 10(6) M(-1)) increased and was also found to remain equal to chloride in the gas and solution phases. The new oblate cavity appeared to hold the HF2(-) in a single east-west arrangement. Our findings demonstrate the promising ability of computer-aided design to fine-tune the structural and electronic match in anion receptors as a means to control the arrangement and binding strength of a desired guest.

1,2,3-Triazoles and the Expanding Utility of Charge Neutral CH···Anion Interactions

As the field of anion supramolecular chemistry continues to grow in its sophistication and understanding of the noncovalent interactions used to effectively bind anions, there exists new theoretical and experimental evidence for a necessary reexamination of the way in which the field views hydrogen bond donors. The heteroatom based hydrogen-bond donors (e.g., NH and OH) are well-known to provide strong stabilization to negatively charged species. However, new findings point to the untapped stabilization energy that lay dormant in extrinsically-activated CH hydrogen bonds. Computational studies showed that an activated aliphatic or aromatic CH can provide an amount of anion stabilization in the gas phase approaching that of conventional NH based donors. Discovery of the Cu(I)-catalyzed Huisgen 1,3-dipolar cycloaddition to provide 1,2,3-triazoles and the ability to readily “click” this functionality into anion receptors has allowed extensive experimental investigation of the ideas posed by these calculations. This chapter will focus on the evolution of the CH hydrogen bond from being viewed as a weak, secondary interaction to now being utilized as a powerful source of anion stabilization in macrocyclic and oligomeric receptors. In addition, the application of the anion binding power of the 1,2,3-triazole towards the preparation of mechanically interlocked structures will also be discussed.

C vs N: Which End of the Cyanide Anion Is a Better Hydrogen Bond Acceptor?

The ability of the C and N ends of the cyanide anion (CN(-)) as acceptors of hydrogen bonds, an experimentally difficult problem, has been computationally examined in this study. Structures obtained in our previous work involving cyanide binding within the cavity of a triazolophane macrocycle (Chem.-Eur. J. 2011, 17, 9123-9129) were used to analyze the problem. Three different approaches involving (a) breakdown of the triazolophane into smaller components, (b) population analyses, and (c) ion-dipole analyses helped demonstrate that the N terminus of cyanide is a slightly better hydrogen bond acceptor than the C terminus even though it is not the site of protonation or covalent bond formation. This outcome reflects a competition between the preference for noncovalent interactions at the nitrogen and covalent bond formation at the carbon.